The death rate from colorectal cancer has declined over the past 15 years due to improved screening methods and advances in treatment. However, risk estimates for recurrence of disease are not very precise and therefore result in considerable undertreatment, as well as overtreatment, of colorectal cancer patients with adjuvant therapy.
The current prognostication in colorectal cancer is based on classic clinicopathological characteristics such as bowel wall invasion, involvement of lymph nodes, and distant organs in metastatic spread. Although useful to discern different survival likelihoods for groups of patients, current prognostication is not able to assess individual risks. For example, the Dukes Staging system describes the following categories of colon cancer patients. In “Dukes Stage A colon cancer,” the cancer has spread beyond the innermost lining of the colon to the second and third layers and involves the inside wall of the colon. The cancer has not spread to the outer wall of the colon or outside the colon. In “Dukes Stage B colon Cancer,” the tumor extends through the muscular wall of the colon, but there is no cancer in the lymph nodes (small structures that are found throughout the body that produce and store cells that fight infection). In “Dukes Stage C colon cancer,” the cancer has spread outside the colon to one or more lymph nodes. Finally, in “Dukes Stage D colon cancer,” the cancer has spread outside the colon to other parts of the body, such as the liver or the lungs. The tumor can be any size and may or may not include affected lymph nodes.
The use of Dukes staging for determination of prognosis and treatment regimen is not optimal for decisions regarding therapy for individual patients, resulting in undertreatment of some colon cancer patients and overtreatment of other colon cancer patients. Dukes staging describes prognosis as follows: Dukes Stage A patients have >90%, Stage B 80%, Dukes C 60% and Dukes D have less than 20% likelihood to remain disease-free 5 years after initial diagnosis. In this regard, the standard of care for node positive patients (Dukes C) is adjuvant chemotherapy using fluorouracil (5-FU) based regimens. However, 50% of these patients would not have developed a recurrence without adjuvant treatment. In patients staged Dukes B (node negative), adjuvant treatment is controversial since the vast majority of the patients are not at risk for recurrence and will thus not benefit from it. Therefore, optimization of treatment would greatly benefit from the ability to accurately classify a patient's prognosis based on the biological potential of a tumor in each individual case.
A marker-based approach to tumor identification and characterization promises improved diagnostic and prognostic reliability. Gene microarrays have been used to identify diagnostic and prognostic biomarkers and to decipher the molecular mechanisms behind the clinical outcome or phenotype in various types of cancers, such as breast cancer. See, e.g., Dai, et al., Cancer Res 65(10):4059-4066 (2005). In the colon cancer area, expression studies have also been conducted which shows interesting leads, but have not yet reached a level where these results can be used to improve treatment decisions for patients. See, for examples, Barrier, et al., Oncogene 26(18):2642-8 (Apr. 19, 2007); Epub (Oct. 9, 2006); Wang, et al., J. Clin Oncol 22(9):1564-71 (May 1, 2004); Epub (Mar. 29, 2004); Eschrich, et al., J. Clin Oncol 23(15):3526-35 (May 20, 2005).
Thus, there exists a need for improved prognostic methods so that appropriate courses of prophylaxis and/or therapy may be provided for colorectal cancer patients.